Production of Sodium Bose--Einstein condensates in an optical dimple trap

We report on the realization of a sodium Bose--Einstein condensate (BEC) in a combined red-detuned optical dipole trap, formed by two beams crossing in a horizontal plane and a third, tightly focused dimple trap propagating vertically. We produce a BEC in three main steps: loading of the crossed dipole trap from laser-cooled atoms, an intermediate evaporative cooling stage which results in efficient loading of the auxiliary dimple trap, and a final evaporative cooling stage in the dimple trap. Our protocol is implemented in a compact setup and allows us to reach quantum degeneracy even with relatively modest initial atom numbers and available laser power

A new hammer to crack an old nut : interspecific competitive resource capture by plants is regulated by nutrient supply, not climate

Peer reviewedPublisher PD

Pulmonary lymphoid tissue induced after SARS-CoV-2 infection in rhesus macaques.

INTRODUCTION: Lung diseases are widespread worldwide. Pulmonary immunity plays a vital role against lung pathogens, including SARS-CoV-2 infection. Understanding the pathogenesis, including the development of local immune responses to infection, is fundamental for developing interventions to control the viral infection. METHODS: Using immunohistochemistry, we investigated the distribution of immune cells in the lungs of rhesus macaques experimentally infected with SARS-CoV-2 and euthanized 11-14 days later. RESULTS: Tertiary lymphoid tissue was found in all SARS-CoV-2 infected animals. The number (13.9 vs 1.5 iPLT number/ lung cm2), size (25992 vs 13946 µm2) and total area (0.46 vs 0.02 mm2 iPLT/ lung cm2) of the lymphoid tissue aggregations were significantly higher in SARS-CoV-2 infected animals than that of normal controls. This induced pulmonary lymphoid tissues comprised B cells, T cells, CD169 macrophages, and follicular dendritic cells with evidence of lymphocyte priming and differentiation. DISCUSSION: The results suggest local immunity plays an important role in the SARS-CoV-2 infection. Further study of pulmonary immunity could lead to new interventions to develop vaccine strategies and discover new immune-regulatory biomarkers in monitoring and controlling SARS-CoV-2 infection and other lung diseases

Situational awareness, relational coordination and integrated care delivery to hospitalized elderly in the Netherlands: A comparison between hospitals

__Abstract__ Background: It is known that interprofessional collaboration is crucial for integrated care delivery, yet we are still unclear about the underlying mechanisms explaining effectiveness of integrated care delivery to older patients. In addition, we lack research comparing integrated care delivery between hospitals. Therefore, this study aims to (i) provide insight into the underlying components 'relational coordination' and 'situational awareness' of integrated care delivery and the role of team and organizational context in integrated care delivery; and (ii) compare situational awareness, relational coordination, and integrated care delivery of different hospitals in the Netherlands. Methods. This cross-sectional study took place in 2012 among professionals from three different hospitals involved in the delivery of care to older patients. A total of 215 professionals filled in the questionnaire (42% response rate).Descriptive statistics and paired-sample t-tests were used to investigate the level of situational awareness, relational coordination, and integrated care delivery in the three different hospitals. Correlation and multilevel analyses were used to investigate the relationship between background characteristics, team context, organizational context, situational awareness, relational coordination and integrated care delivery. Results: No differences in background characteristics, team context, organizational context, situational awareness, relational coordination and integrated care delivery were found among the three hospitals. Correlational analysis revealed that situational awareness (r = 0.30; p < 0.01), relational coordination (r = 0.17; p < 0.05), team climate (r = 0.29; p < 0.01), formal internal communication (r = 0.46; p < 0.01), and informal internal communication (r = 0.36; p < 0.01) were positively associated with integrated care delivery. Stepwise multilevel analyses showed that formal internal communication (p < 0.001) and situational awareness (p < 0.01) were associated with integrated care delivery. Team climate was not significantly associated with integrated care delivery when situational awareness and relational coordination were included in the equation. Thus situational awareness acted as mediator between team climate and integrated care delivery among professionals delivering care to older hospitalized patients. Conclusions: The results of this study show the importance of formal internal communication and situational awareness for quality of care delivery to hospitalized older patients

Correction: Exome Sequencing in an Admixed Isolated Population IndicatesNFXL1 Variants Confer a Risk for Specific Language Impairment

Children affected by Specific Language Impairment (SLI) fail to acquire age appropriate language skills despite adequate intelligence and opportunity. SLI is highly heritable, but the understanding of underlying genetic mechanisms has proved challenging. In this study, we use molecular genetic techniques to investigate an admixed isolated founder population from the Robinson Crusoe Island (Chile), who are affected by a high incidence of SLI, increasing the power to discover contributory genetic factors. We utilize exome sequencing in selected individuals from this population to identify eight coding variants that are of putative significance. We then apply association analyses across the wider population to highlight a single rare coding variant (rs144169475, Minor Allele Frequency of 4.1% in admixed South American populations) in the NFXL1 gene that confers a nonsynonymous change (N150K) and is significantly associated with language impairment in the Robinson Crusoe population (p = 2.04 × 10–4, 8 variants tested). Subsequent sequencing of NFXL1 in 117 UK SLI cases identified four individuals with heterozygous variants predicted to be of functional consequence. We conclude that coding variants within NFXL1 confer an increased risk of SLI within a complex genetic model

Prostaglandin E receptor EP4 is a therapeutic target in breast cancer cells with stem-like properties

The cyclooxygenase pathway is strongly implicated in breast cancer progression but the role of this pathway in the biology of breast cancer stem/progenitor cells has not been defined. Recent attention has focused on targeting the cyclooxygenase 2 (COX-2) pathway downstream of the COX-2 enzyme by blocking the activities of individual prostaglandin E (EP) receptors. Prostaglandin E receptor 4 (EP4) is widely expressed in primary invasive ductal carcinomas of the breast and antagonizing this receptor with small molecule inhibitors or shRNA directed to EP4 inhibits metastatic potential in both syngeneic and xenograft models. Breast cancer stem/progenitor cells are defined as a subpopulation of cells that drive tumor growth, metastasis, treatment resistance, and relapse. Mammosphere-forming breast cancer cells of human (MDA-MB-231, SKBR3) or murine (66.1, 410.4) origin of basal-type, Her-2 phenotype and/or with heightened metastatic capacity upregulate expression of both EP4 and COX-2 and are more tumorigenic compared to the bulk population. In contrast, luminal-type or non-metastatic counterparts (MCF7, 410, 67) do not increase COX-2 and EP4 expression in mammosphere culture. Treatment of mammosphere-forming cells with EP4 inhibitors (RQ-15986, AH23848, Frondoside A) or EP4 gene silencing, but not with a COX inhibitor (Indomethacin) reduces both mammosphere-forming capacity and the expression of phenotypic markers (CD44(hi)/CD24(low), aldehyde dehydrogenase) of breast cancer stem cells. Finally, an orally delivered EP4 antagonist (RQ-08) reduces the tumor-initiating capacity and markedly inhibits both the size of tumors arising from transplantation of mammosphere-forming cells and phenotypic markers of stem cells in vivo. These studies support the continued investigation of EP4 as a potential therapeutic target and provide new insight regarding the role of EP4 in supporting a breast cancer stem cell/tumor-initiating phenotype

The Chemokine Receptor CXCR3 Isoform B Drives Breast Cancer Stem Cells

We are seeking to identify molecular targets that are relevant to breast cancer cells with stem-like properties. There is growing evidence that cancer stem cells (CSCs) are supported by inflammatory mediators expressed in the tumor microenvironment. The chemokine receptor CXCR3 binds the interferon-γ-inducible, ELR-negative CXC chemokines CXCL9, CXCL10, and CXCL11 and malignant cells have co-opted this receptor to promote tumor cell migration and invasion. There are 2 major isoforms of CXCR3: CXCR3A and CXCR3B. The latter is generated from alternative splicing and results in a protein with a longer N-terminal domain. CXCR3 isoform A is generally considered to play a major role in tumor metastasis. When the entire tumor cell population is examined, CXCR3 isoform B is usually detected at much lower levels than CXCR3A and for this, and other reasons, was not considered to drive tumor progression. We have shown that CXCR3B is significantly upregulated in the subpopulation of breast CSCs in comparison with the bulk tumor cell population in 3 independent breast cancer cell lines (MDA-MB-231, SUM159, and T47D). Modulation of CXCR3B levels by knock in strategies increases CSC populations identified by aldehyde dehydrogenase activity or CD44+CD24− phenotype as well as tumorsphere-forming capacity. The reverse is seen when CXCR3B is gene-silenced. CXCL11 and CXCL10 directly induce CSC. We also report that novel CXCR3 allosteric modulators BD064 and BD103 prevent the induction of CSCs. BD103 inhibited experimental metastasis. This protective effect is associated with the reversal of CXCR3 ligand-mediated activation of STAT3, ERK1/2, CREB, and NOTCH1 pathways. We propose that CXCR3B, expressed on CSC, should be explored further as a novel therapeutic target

Sodium channel Nav1.8 immunoreactivity in painful human dental pulp.

Background: The tetrodotoxin-resistant voltage-gated sodium channel Nav1.8 (SNS1/PN3) is expressed by nociceptors and may play a role in pain states. Methods: Using specific antibodies for immunohistochemistry, we studied Nav1.8 – immunoreactivity in human dental pulp in relation to the neuronal marker neurofilament. Human tooth pulp was extracted from teeth harvested from a total of twenty-two patients (fourteen without dental pain, eight patients with dental pain). Results: Fibres immunoreactive for Nav1.8, were significantly increased on image analysis in the painful group: median (range) Nav1.8 to Neurofilament % area ratio, non-painful 0.059 (0.006–0.24), painful 0.265 (0.13–0.5), P = 0.0019. Conclusion: Nav1.8 sodium channels may thus represent a therapeutic target in trigeminal nerve pain states

The Volunteer Satisfaction Index: A Validation Study in the Chinese Cultural Context

Using a Hong Kong-sourced sample of 261 participants, this study set out to validate the Volunteer Satisfaction Index (VSI) in the Chinese cultural context and to evaluate its psychometric properties. The VSI was originally developed by Galindo-Kuhn and Guzley (2001) to measure the outcomes of volunteer experiences. In this study, exploratory factor analysis (EFA) yielded a different factor structure from that proposed by the scale developer. The three factors found were personal gain, relationship within organization and relationship with peers. Cronbach’s alpha values were high for all three subscales. Results from correlation and regression analysis also confirmed the construct and criterion-related validity of the scale. Thus, the reliability and validity of the scale were confirmed. Implications for the assessment of volunteer satisfaction and further directions for cross-cultural studies on related topics are discussed

Unhappy patients are not alike: Content analysis of the negative comments from China's good doctor website

Background: With the rise in popularity of Web 2.0 technologies, the sharing of patient experiences about physicians on online forums and medical websites has become a common practice. However, negative comments posted by patients are considered to be more influential by other patients and physicians than those that are satisfactory. Objective: The aim of this study was to analyze negative comments posted online about physicians and to identify possible solutions to improve patient satisfaction, as well as their relationship with physicians. Methods: A Java-based program was developed to collect patient comments on the Good Doctor website, one of the most popular online health communities in China. A total of 3012 negative comments concerning 1029 physicians (mean 2.93 [SD 4.14]) from 5 highly ranked hospitals in Beijing were extracted for content analysis. An initial coding framework was constructed with 2 research assistants involved in the codification. Results: Analysis, based on the collected 3012 negative comments, revealed that unhappy patients are not alike and that their complaints cover a wide range of issues experienced throughout the whole process of medical consultation. Among them, physicians in Obstetrics and Gynecology (606/3012, 20.12%; P=.001) and Internal Medicine (487/3012, 16.17%; P=.80) received the most negative comments. For negative comments per physician, Dermatology and Sexually Transmitted Diseases (mean 5.72, P<.001) and Andrology (mean 5, P=.02) ranked the highest. Complaints relating to insufficient medical consultation duration (577/3012, 19.16%), physician impatience (527/3012, 17.50%), and perceived poor therapeutic effect (370/3012, 12.28%) received the highest number of negative comments. Specific groups of people, such as those accompanying older patients or children, traveling patients, or very important person registrants, were shown to demonstrate little tolerance for poor medical service. Conclusions: Analysis of online patient complaints provides an innovative approach to understand factors associated with patient dissatisfaction. The outcomes of this study could be of benefit to hospitals or physicians seeking to improve their delivery of patient-centered services. Patients are expected to be more understanding of overloaded physicians' workloads, which are impacted by China's stretched medical resources, as efforts are made to build more harmonious physician-patient relationships.National Natural Science Foundation of China; Hubei Social Science Foundation; Fundamental Research Funds for the Central Universitie